Duan Kaiti, Dash Biraja C, Sasson Daniel C, Islam Sara, Parker Jackson, Hsia Henry C
Section of Plastic Surgery, Department of Surgery Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Bioengineering (Basel). 2021 Dec 18;8(12):223. doi: 10.3390/bioengineering8120223.
Tissue-engineered constructs have immense potential as autologous grafts for wound healing. Despite the rapid advancement in fabrication technology, the major limitation is controlling angiogenesis within these constructs to form a vascular network. Here, we aimed to develop a 3D hydrogel that can regulate angiogenesis. We tested the effect of fibronectin and vascular smooth muscle cells derived from human induced pluripotent stem cells (hiPSC-VSMC) on the morphogenesis of endothelial cells. The results demonstrate that fibronectin increases the number of EC networks. However, hiPSC-VSMC in the hydrogel further substantiated the number and size of EC networks by vascular endothelial growth factor and basic fibroblast growth factor secretion. A mechanistic study shows that blocking αvβ3 integrin signaling between hiPSC-VSMC and fibronectin impacts the EC network formation via reduced cell viability and proangiogenic growth factor secretion. Collectively, this study set forth initial design criteria in developing an improved pre-vascularized construct.
组织工程构建体作为用于伤口愈合的自体移植物具有巨大潜力。尽管制造技术取得了快速进展，但主要限制在于控制这些构建体内的血管生成以形成血管网络。在此，我们旨在开发一种能够调节血管生成的三维水凝胶。我们测试了纤连蛋白和源自人诱导多能干细胞的血管平滑肌细胞（hiPSC-VSMC）对内皮细胞形态发生的影响。结果表明，纤连蛋白增加了内皮细胞网络的数量。然而，水凝胶中的hiPSC-VSMC通过分泌血管内皮生长因子和碱性成纤维细胞生长因子进一步证实了内皮细胞网络的数量和大小。一项机制研究表明，阻断hiPSC-VSMC与纤连蛋白之间的αvβ3整合素信号传导会通过降低细胞活力和促血管生成生长因子分泌来影响内皮细胞网络形成。总体而言，本研究提出了开发改进的预血管化构建体的初步设计标准。
